Electrical Activity of the Heart

cardiovascular system is composed of two parts

• the heart: a pump

• the blood vessels: a set of tubes connected to the pump

what are the two parts of the circulatory system?

pulmonary and systemic

pulmonary circulation

the right side of the heart pumps blood to the pulmonary circulation and the left side of the heart receives blood from the pulmonary circulation

systemic circulation

the left side of the heart pumps blood to the systemic circulation and the right side of the heart receives blood from the systemic circulation

the cardiovascular system is comprised of what two pumps in series?

- the right side of the heart is a low pressure pump which pumps to the pulmonary system

- the left side of the heart is a high pressure pump which pumps to the systemic circulation

circulation of the venous system vs the arterial system?

venous = 64%

arterial = 29%:

- arteries = 13%:

-- arterioles/capillaries 7%

-- pulmonary circ 7%

circulation can be broken down into

• arteries

• arterioles

• capillaries

• veins

arteries

these blood vessels bring blood from the heart to the tissues

arterioles are surrounded by? which affects them how?

these blood vessels are surrounded by smooth muscle. Contraction of the smooth muscle changes the diameter of the blood vessel which affects blood pressure

capillaries

these blood vessels are the site of nutrient and waste exchange

veins

these blood vessels bring blood from the tissues back to the heart

systemic circulation contains a number of capillary beds arranged how?

• parallel: most beds are arranged this way

• series: kidney capillaries contains two capillaries in series (glomerular capillary and peritubular capillary) and the gastro-intestinal capillaries are in series with the liver capillaries

Capillaries are found within what distance of most cells in the body? This is important because?

50um, O2 moves from the blood into the interstitial compartment via diffusion

Most of the blood is found in the? what are the percentages?

veins; The veins contain approximately 64% of the blood whereas the arteries and arterioles contain approximately 16% of the blood

transport function of the circulation

1. the circulation brings oxygen from the lungs and nutrients from the gastrointestinal system and liver to the cells in the body.

2. the circulation removes waste products such as CO2 (via the lungs) or urea (via the kidneys).

3. the circulation transports various substances, such as hormones, immune cells, antibodies, clotting proteins and stored nutrients, from one cell in the body to another.

4. the circulation helps dissipate or conserve heat

heart and circulation together regulate what?

help to maintain blood pressure and blood volume which in turn allow oxygen to reach tissues

pulsitile pressure

- generated by the heart

1. pacemaker cells: automatic electrical rhythm nodal cells, generate periodic action potentials (70bpm)

2. conducting cells: spread the AP through the heart, causing periodic contraction of the heart via:

3. contracting cells: contracts the heart

periodic contraction of the heart generates periodic, pulsatile pressure

pulse of pressure

the difference between the highest pressure developed in a beat and the lowest pressure

pulse of pressure travels how?

travels from the heart throughout the vasculature, from the aorta to the arteries, to the arterioles, to the capillaries, to the veins and back to the heart

pressure pulse is largest in the?

heart

- Before the heart contracts the pressure is close to zero

- As the heart ejects blood the pressure reaches its maximum at about 120 mm Hg

The size of the pressure pulse is substantially decreased by the ____ and further decreased by the ____

aorta; arteries

By the time the pressure pulse reaches the arterioles and the capillaries the pressure pulse is?

close to zero

- there is no fluctuation in pressure from one heartbeat to the next

- This insures a continuous flow of blood through the capillaries

The pressure in the capillaries is ____ than the pressure in the arteries, but is not?

lower; the pressure in the capillaries is not zero. This non-zero pressure is what drives O2 into the tissues

The pressure in the veins and on the right side of the heart is?

close to zero;

in a normal, healthy individual, the maximum pressure difference at between the left side of the heart and the right side of the heart is?

about 120 mm Hg (i.e.𝑃𝑎𝑜𝑟𝑡𝑎𝑝𝑒𝑎𝑘 −𝑃𝑣𝑒𝑖𝑛𝑠 = 120 𝑚𝑚 𝐻𝑔)

pressure pulse in the pulmonary circulation

- similar to pressures in the systemic

- there is a pressure pulse in the right ventricle due to the pulsitile nature of the electrical rhythm

- this pressure pulse decreases from the pulmonary arteries to the pulmonary veins

sympathetic control on HR, contraction, and BVs

SA/AV node - increases HR

ventricular muscle - increases contraction

BVs - vasoconstriction

parasympathetic control on HR, contraction, and BVs

SA/AV node - decreases HR

atrial muscle - decreases contraction

BVs - minimal

At resting heart rates (approximately 60-70 beats per minute) both the parasympathetic system and the sympathetic system are?

active

at resting HR, which ANS system is stronger influence? what does this mean?

PSNS;

severing parasympathetic nerves to the heart will increase resting heart rate to a greater extent than severing sympathetic nerves would decrease heart rate

Pump strength is under control by mainly the?

sympathetic system

There is some parasympathetic control of ____, but because most of the blood is pumped from the heart as a result of _____, there is little parasympathetic effect on the strength of contraction of the ventricles

atrial muscle; ventricular contraction

Blood vessel diameter is under control by mainly?

the sympathetic system

rhythmic electrical activity originates in a region of the heart called the?

sino-atrial node (SA node)

SA node

collection of cells near the right atrium

the electrical signal propagates from the SA node to the?

through the atria and possibly through internodal pathways in the atria toanother collection of cells called the atrio-ventricular node (AV node)

from the AV node, the signals spreads through?

spreads throughout the ventricles via the bundle of His and Purkinje fibers, ultimately resulting in ventricular contraction and ejection of blood from the heart.

cell types of the heart

- pacemaker cells

- conducting cells

- contracting cells

pacemaker cells

which set the automatic rhythm of the heart and allow it to beat continuously throughout a lifetime. These cells are found in the SA and AV node

conducting cells

conduct the electrical signal (an action potential) from one part of the heart to another. These cells are found in the bundle of His, the bundle branches and the Purkinje fiber network

contracting cells

generate pressure within the heart and pump blood out of the heart. These cells make up most of the cells in the walls of the atria and the ventricle. Contracting cells are called myocytes and make up about 75% of the total volume of the heart.

pacemaker action potential

- found in sino-atrial and the atrio-ventricular nodes

- type is autorhythmic: these cells generate the same action potential periodically for long periods of time

contracting/conducting action potential

- found in ventricular myocytes, atrial myocytes, cells in the bundleof His and the Purkinje fibers

- contract in response to an action potential or conduct the action potential to neighboring cells

sodium nernst potential in the heart

EC - 145

IC - 10

Nernst - +71

potassium nernst potential in the heart

EC - 2

IC - 135

Nernst - -94

calcium nernst potential in the heart

EC - 2

IC - 10^-4

Nernst - 132

depolarization

the inside of the cell becoming more positive

hyperpolarization

the inside of the call becoming more negative

repolarization

the inside of the cell becoming more negative after first becoming positive. This is most often used to describe the hyperpolarization part of the action potential that occurs after the membrane has depolarized to a value close to the Nernst for sodium.

most important ions in the heart

sodium, potassium, and calcium

phase 0

upstroke

- cell depolarizes as a result of the spread of an AP from a neighboring cell

- opens fast voltage-gated sodium channels

- leads to further depolarization which opens up more voltage-gated sodium channels

phase 1

early repolarization

- the cell slightly hyperpolarizes due to the opening of voltage gated potassium channels and inactivation of voltage gated sodium channels

- potassium channel involved in this phase is one of the 2 basic types of voltage-gated potassium channels, and is referred to as Type I

phase 2

plateau

- voltage remains near 0 mV due to a second type of voltage-gated potassium channels and voltage gated calcium channels

- since both are open, the MP is somewhere bw -94 and +132

phase 3

repolarization

- towards end of phase 2 and during this pase the voltage gated calcium channels inactivate

- voltage gated potassium channels dominate so the MP hyperpolarizes towards the Nernst for K -94mV

phase 4

resting membrane potential

- MP when there is no action potential

- it is negative and is due to potassium channels which are open at any MP (leak channels)

All four types of voltage-gated channels discussed in the conducting/contracting action potential (2 K+, 1 Na+, 1 Ca2+) are?

depolarization activated channels

phase 0 channels

open - Na+, K+I, Ca2+, K+II

phase 1 channels

open - K+I, Ca2+, K+II

inactive - Na+

phase 2 beginning channels

open - Ca2+, K+II

inactive -Na+, K+I,

phase 2 end channels

open - K+II

inactive - Ca2+

phase 3 channels

open - K+II

inactive - Ca2+, Na+, K+I

phase 4 channels

closed - Na+, K+I, Ca2+, K+II

conductance

number of open channels

sodium conductance

increases rapidly as the sodium channels rapidly open and then decreases as the sodium channels inactivate

potassium type I conductance

increases rapidly, (but slower than for sodium channels), as the potassium channels open and then decreases rapidly as the potassium channels inactivate.

calcium conductance

increases more slowly as the calcium channels open and then decreases as the calcium channels inactivate

potassium type II

increases even more slowly than for calcium channels as the potassium channels open and then decreases as the potassium channels close

what channels does not deactivate?

K+ type II

the membrane potential depends on

relative number of open channels and the Nernst potentials for the different ions

During the plateau phase the membrane potential is determined by

approximately equal numbers of L-type Ca2+ channels and K+ type II channels

During the repolarization phase the membrane potential is determined by

mostly K+ type II channels and some L-type Ca2+ channels

pacemaker AP phases

phase 0 - upstroke

phase 3 - repolarization

phase 4 - slow depolarization

pacemaker AP: phase 0

upstroke

- upstroke in the pacemaker action potential is due to the opening of voltage-gated calcium channels (there are no fast voltage-gated sodium channels).

- These voltage-gated calcium channels are referred to as L-type calcium channels as opposed to T-type which are involved in phase 4.

- This depolarizes the cell towards the Nernst potential for calcium (+132 mV) and opens up more voltage-gated calcium channels

pacemaker AP: phase 3

repolarization

- voltage gated calcium channels inactivate and the voltage gated potassium channels open.

- the membrane is dominated by potassium channels and the cell hyperpolarizes towards the Nernst potential for potassium (-94 mV).

pacemaker AP: phase 4 channel 1

slow depolarization: sodium

- a special kind of voltage-gated sodium channel (often denoted in the literature as If - "I" for current and "f" for funny because it is different than most other voltage-gated channels) opens.

- This channel opens when the membrane hyperpolarizes and closes when the membrane depolarizes.

- This type of voltage-gated sodium channel responds to voltage in the opposite way compared to the voltage-gated sodium channels in the contracting and conducting cells.

- channel opens at the beginning of phase 4 and closes at the end of phase 4

pacemaker AP: phase 4 channel 2

slow depolarization: calcium

- 2nd type of voltage-gated calcium channel, referred to as T-type calcium channels, opens.

- This works together with the closing of the special voltage-gated channel to depolarize the cell

what happens to the membrane when Na+ channels and T-type Ca2+ channels open

depolarizes

what happens to the membrane when L-type Ca2+ channels open

further depolarizes

what happens to the membrane when K+ open

hyperpolarizes

what happens to the membrane when Na+ channels and T-type Ca2+ channels open a second time

depolarizes and the cycle starts again

The Na+-channels are ___ at the beginning of phase 4, but start to ___ as the membrane depolarizes and so are?

open; close; mostly closed at the end of phase 4

T-type Ca2+ channels start to ___ during phase 4 and so are ___ at the beginning of phase 4 and then ___ at the end of phase 4

open; closed; open

calcium T and L conductance

increases as the calcium channels open( more slowly than the sodium channels in the conducting and contracting action potential) and then decreases as the calcium channels inactivate

potassium pacemaker conductance

increases slowly as the potassium channels open and then decreases as the potassium channels close

sodium pacemaker conductance

as the membrane potential hyperpolarizes at the end of the action potential the sodium conductance due to this special channel increases. This depolarizes the membrane bringing it towards threshold, which decreases the sodium conductance

which pacemaker channels open due to depolarization?

T-type Ca2+, L-type Ca2+, K+

what pacemaker channel opens due to hyperpolarization?

Na+

what pacemaker channels inactivate

T-type Ca2+, L-type Ca2+

During the upstroke of the pacemaker action potential the membrane potential is determined mostly by

L-type Ca2+ channels and by some K+ channels

Close to the resting membrane potential, the membrane potential is determined by

mostly K+ type II channels

Na+ is the only voltage-gated cardiac channel that opens with?

the opposite sign of voltage

voltage-gated channels in the heart can be categorized into what two basic types?

1. channels with one gate

2. channels with 2 gates

channels with one gate

only opens and closes: C

1. voltage-gated potassium channel that repolarizes the membrane (type II).

2. the special type of voltage gated sodium channel that is opened by membrane hyperpolarization and closed by depolarization.

channels with 2 gates

opens and then inactivates. The transition from closed to open is accomplished by one gate and the transition from open to inactivated is accomplished by a second gate. C

what are the channels with two gates?

1. fast voltage-gated sodium channel involved in the upstroke of the ventricular action potential.

2. slow voltage-gated calcium channel involved in initial depolarization of the pacemaker action potential (T-type)

3. slow voltage-gated calcium channel involved in the upstroke of the pacemaker action potential (L-type).

4. voltage-gated potassium channel involved in the early repolarization of the ventricular action potential (type I).

gap junction

- contact between heart muscle cells

- region of very close apposition between 3 cells

- the gap is roughly 3 nm wide

- the junction contains an number of different types of proteins

- one important protein is an ion channel, which allows small molecules up to about1000 KDa (i.e. from ions up to small molecules such as cAMP) to pass through. One half of the channel is located in each cell

spread of an AP between pacemaker cells

1. Influx of sodium and calcium depolarizes the cell during phase 0 or phase 4 of the pacemaker action potential.

2. The sodium and calcium ions then diffuse down their electrochemical gradients through gap junctions to a neighboring cell. In the above example the pacemaker cell is to the left is depolarized and the neighboring pacemaker cell is at rest. As a result, there is an electrical gradient from the cell on the left (positive inside) to the cell on the right (negative inside)

3. The sodium and calcium ions that have diffused to the cell on the right will depolarize the cell on the right. This will open the voltage gated ion channels in that cell and will trigger and action potential in that cell

if a pacemaker cell is connected via gap junctions to a conducting cell, then the pacemaker cell will fire a? and what occurs?

pacemaker action potential, sodium and calcium will then diffuse into the conducting cell and the conducting cell will fire a conducting/contracting action potential

rate of AP propagation throughout the heart

1. origin SA node 0.05 ms

2. Atria 1 ms

3. AV node 0.05 ms

4. Bundle of His 1ms

5. purkinje fibers 4ms

6. ventricles 1ms

the velocity of the AP through the AV node is ____, allowing?

slow; allowing time for the signal to completely spread throughout the atria before the signal starts to spread through the ventricles, allowing enough time for the atria to contract and empty blood into the ventricles